Our objective is to study the DNA damage and repair in various individual genes and in non-coding sequences with the genome. This is correlated to more traditional studies of DNA repair as an average over the genome. It is now established that there is intragenomic heterogeneity of DNA repair. Findings have indicated that active genes are preferentially repaired in mammalian cells and that determinations of DNA repair in specific genes are important for correlations to biological endpoints and to risk assessments. We now have now established methods to study DNA damage and repair after various carcinogens and cancer chemotherapeutics. We are studying the DNA repair of genes in a number of human, cancer prone DNA repair deficient syndromes and in various human and rodent mutant cell lines, some of which are transfected with repair genes. We are studying DNA repair levels in parts of the genome that are known to be prone to high levels of mutation or rearrangements in an attempt to establish correlations between genomic instability and DNA repair deficiency. We are also investigating the role of DNA repair in multidrug resistance.